Wada Y, Etoh Y, Ohira A, Tsukamoto M, Nakamura M
Nihon Yakurigaku Zasshi. 1982 Jan;79(1):43-55.
It has been previously reported that acemetacin (ACM), the carboxymethyl ester of indomethacin (IND), is almost completely metabolized to IND in vivo. In the present study, the anti-inflammatory effects of ACM were compared with those of IND. ACM showed inhibitory effects on vascular permeability induced by phenylquinone. ACM inhibited carrageenin, kaolin, and nystatin edema dose-dependently and the ED30 in the carrageenin edema test was 2.8 Mg/kg. Inhibitory effects of ACM on carrageenin edema was not influenced by adrenalectomy or repeated administration of ACM. ACM also inhibited ultraviolet erythema at 5 mg/kg. Furthermore, ACM significantly inhibited granuloma formation at 2.5 mg/kg/day. The ED30 for the therapeutic effect on established adjuvant arthritis was 0.33 mg/kg/day. These anti-inflammatory effects of orally administered ACM were equivalent to or somewhat weaker than those of IND at an equimolar dose. Platelet aggregation was inhibited when ACM was given orally to rats and the activity of ACM was similar to that of IND. On the other hand, the effects of locally administered ACM on carrageenin and kaolin edema were markedly less potent than those of IND. In addition, inhibitory effects on prostaglandin synthesis and platelet aggregation in vitro were significantly weaker than those of IND. These results that the observed anti-inflammatory effects orally administered ACM are not due to its inherent action, but due to its metabolite, IND.
先前已有报道称，消炎痛（IND）的羧甲基酯阿西美辛（ACM）在体内几乎完全代谢为IND。在本研究中，对ACM和IND的抗炎作用进行了比较。ACM对苯醌诱导的血管通透性有抑制作用。ACM对角叉菜胶、高岭土和制霉菌素所致水肿有剂量依赖性抑制作用，在角叉菜胶性水肿试验中的ED30为2.8mg/kg。ACM对角叉菜胶性水肿的抑制作用不受肾上腺切除术或重复给药的影响。ACM在5mg/kg时也能抑制紫外线红斑。此外，ACM在2.5mg/kg/天的剂量下能显著抑制肉芽肿形成。对已建立的佐剂性关节炎的治疗作用的ED30为0.33mg/kg/天。口服ACM的这些抗炎作用在等摩尔剂量下与IND相当或略弱。给大鼠口服ACM时血小板聚集受到抑制，且ACM的活性与IND相似。另一方面，局部给予ACM对角叉菜胶和高岭土性水肿的作用明显弱于IND。此外，体外对前列腺素合成和血小板聚集的抑制作用明显弱于IND。这些结果表明，口服ACM所观察到的抗炎作用并非因其固有作用，而是因其代谢产物IND所致。
